Background
Few studies have investigated the incidence of anaphylaxis induced by individual or structurally similar cephalosporins. The aims of the study were to assess the incidence of ...cephalosporin‐induced anaphylaxis and evaluate the clinical efficacy of screening skin tests.
Methods
In this retrospective cohort study, we obtained information on total cephalosporin use and cephalosporin‐induced anaphylaxis in intravenous cephalosporin recipients in 12 general hospitals between 2013 and 2015. Cephalosporins were divided into 4 groups according to similar side‐chain structures. The incidence of cephalosporin‐induced anaphylaxis was assessed for each cephalosporin, cephalosporin generation, and side‐chain group. To verify the efficacy of screening intradermal tests (IDT) with cephalosporin, the 12 hospitals were assigned to the intervention or control group depending on whether they performed screening IDT before the administration of cephalosporins.
Results
We identified 76 cases of cephalosporin‐induced anaphylaxis with 1 123 345 exposures to intravenous cephalosporins (6.8 per 100 000 exposures), and the incidence of fatal anaphylaxis by cephalosporin was 0.1 cases per 100 000 exposures. The highest incidences of anaphylaxis occurred in the ceftizoxime (13.0 cases per 100 000 exposures) and side‐chain group 1 (cefepime, cefotaxime, ceftizoxime, ceftriaxone, and cefuroxime; 9.3 per 100 000). There was no case of anaphylaxis induced by cefoxitin, cefmetazole, cefminox, and cefotiam. The clinical effectiveness of routine screening IDT was not significant (P = .06).
Conclusions
The incidence of cephalosporin‐induced anaphylaxis differed according to individual drugs and side‐chain structure. Screening IDT showed no clinical efficacy at a population level.
Among total 1 140 354 cephalosporin treatment courses from 12 hours hospitals, the incidence of cephalosporin induced anaphylaxis was 6.8 per 100 000 exposures and the related fatality was 1.3%. The incidence of cephalosporin induced anaphylaxis varies with each drug type, and the highest incidences of anaphylaxis occurred in the ceftizoxime (13.0 cases per 100 000 exposures). Screening intradermal tests with cephalosporin failed to show preventive effect on cephalosporin‐induced anaphylaxis.
Aims
The contribution of glycaemic variability to the microvascular complication of diabetes has not been established. We examined whether there is an independent association between indices of ...glycaemic variability in continuous glucose monitoring and extent of albuminuria.
Methods
A total of 173 patients with Type 2 diabetes (without insulin therapy, n = 96; with insulin therapy, n = 77) who had unexplained large fluctuations in blood glucose values underwent three‐day continuous glucose monitoring. We used a multinomial logistic regression model to determine whether the indices of glycaemic variability independently affected the odds of having a spot urine albumin/creatinine ratio of 30–299 mg/g and ≥ 300 mg/g.
Results
Higher standard deviation (P = 0.002), mean of daily differences (P = 0.023) and mean amplitude of glycaemic excursion (P = 0.043) significantly increased the odds of having a urine albumin/creatinine ratio of ≥ 300 mg/g. In multivariable analysis, only higher standard deviation, but not mean amplitude of glycaemic excursion and mean of daily differences, independently increased the odds of having a urine albumin/creatinine ratio of ≥ 300 mg/g (P = 0.025). Coefficient of variation (sd/mean) was not associated with the odds of having a urine albumin/creatinine ratio of 30–299 or ≥ 300 mg/g.
Conclusions
The independent association between standard deviation and the extent of albuminuria was lost when the measures were normalized by mean glucose level. At least in terms of relative measures of glycaemic variability, we failed to demonstrate an independent association between glycaemic variability and albuminuria extent in patients with inadequately controlled Type 2 diabetes.
What's new?
The contribution of glycaemic variability to the microvascular complication of diabetes has not been established.
We examined whether there is an independent association between indices of glycaemic variability in continuous glucose monitoring and extent of albuminuria.
This is the first continuous glucose monitoring‐based study to explore an association between various measures of glycaemic variability and degree of microvascular complication in a large clinical database composed of patients with inadequately controlled Type 2 diabetes.
The results of this study underline the importance of considering the contribution of mean glucose to the glycaemic variability indices, which has been frequently overlooked in the previous studies.
Background and purpose
High blood pressure (BP) at presentation is associated with poor outcomes in acute ischaemic stroke, but serial BP measurements may better delineate the clinical implications ...of BP. The aim was to investigate the association between various BP parameters and functional outcomes in acute ischaemic stroke patients treated with endovascular thrombectomy (EVT).
Methods
This study reports a retrospective analysis of a prospective registry of a comprehensive stroke centre. Patients treated with EVT due to large vessel occlusion in the anterior circulation were enrolled. BP was measured hourly during the first 24 h after admission. Associations of various BP parameters, including BP variability, with functional outcomes at 3 months, including good outcomes (modified Rankin Scale score of 0–2), were analysed.
Results
Of the 378 enrolled patients (mean age 70 ± 11 years, male 54.2%), 313 (82.8%) achieved successful reperfusion after EVT, and 149 (39.4%) had good outcomes at 3 months. Higher mean systolic BP each 10 mmHg increase, odds ratio 0.82 (0.69–0.97) and higher systolic successive variation (SV) each 10% increase, odds ratio 0.37 (0.18–0.76) were associated with a reduced likelihood of achieving good outcomes. In addition, reperfusion status after EVT moderated the influence of higher systolic SV on good outcomes (Pint = 0.05).
Conclusion
The results showed that a higher mean systolic BP and systolic SV during the first 24 h of EVT reduced the likelihood of good outcomes at 3 months. The effects of these parameters on outcomes are more substantial amongst patients with successful reperfusion after EVT, suggesting that different BP control strategies should be employed according to reperfusion status.
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Despite remarkable progress in cutaneous melanoma genomic profiling, the mutational landscape of primary mucosal melanomas (PMM) remains unclear. Forty-six PMMs underwent targeted exome sequencing of ...111 cancer-associated genes. Seventy-six somatic nonsynonymous mutations in 42 genes were observed, and recurrent mutations were noted on eight genes, including TP53 (13%), NRAS (13%), SNX31 (9%), NF1 (9%), KIT (7%) and APC (7%). Mitogen-activated protein kinase (MAPK; 37%), cell cycle (20%) and phosphatidylinositol 3-kinase (PI3K)-mTOR (15%) pathways were frequently mutated. We biologically characterized a novel ZNF767-BRAF fusion found in a vemurafenib-refractory respiratory tract PMM, from which cell line harboring ZNF767-BRAF fusion were established for further molecular analyses. In an independent data set, NFIC-BRAF fusion was identified in an oral PMM case and TMEM178B-BRAF fusion and DGKI-BRAF fusion were identified in two malignant melanomas with a low mutational burden (number of mutation per megabase, 0.8 and 4, respectively). Subsequent analyses revealed that the ZNF767-BRAF fusion protein promotes RAF dimerization and activation of the MAPK pathway. We next tested the in vitro and in vivo efficacy of vemurafenib, trametinib, BKM120 or LEE011 alone and in combination. Trametinib effectively inhibited tumor cell growth in vitro, but the combination of trametinib and BKM120 or LEE011 yielded more than additive anti-tumor effects both in vitro and in vivo in a melanoma cells harboring the BRAF fusion. In conclusion, BRAF fusions define a new molecular subset of PMM that can be targeted therapeutically by the combination of a MEK inhibitor with PI3K or cyclin-dependent kinase 4/6 inhibitors.
Micro (mi)RNAs are small, highly conserved noncoding RNAs that control gene expression post-transcriptionally either via the degradation of target mRNAs or the inhibition of protein translation. Each ...miRNA is believed to regulate the expression of multiple mRNA targets, and many miRNAs have been linked to the initiation and progression of human cancer. miRNAs control various activities of the immune system and different stages of hematopoietic development, and their misexpression is the cause of various blood malignancies. Certain miRNAs have oncogenic activities, whereas others have the potential to act as tumor suppressors. Because they control fundamental processes such as differentiation, cell growth and cell death, the study of the role of miRNAs in human neoplasms holds great promise for novel forms of therapy. Here, we summarize the role of miRNAs and their targets in contributing to human cancers and their function as regulators of apoptotic pathways and the immune system.
Summary
Background
Asthma in the elderly (aged ≥ 65 years old) is a significant concern with high morbidity, but the pathophysiology remains unclear particularly in late‐onset asthma. Recent studies ...suggest staphylococcal enterotoxin IgE (SE‐IgE) sensitization to be a risk factor for asthma in general populations; however, the associations have not been examined in late‐onset elderly asthma.
Objective
We aimed to examine the associations of SE‐IgE sensitization with late‐onset asthma in the elderly, using a database of elderly asthma cohort study.
Methods
A total of 249 elderly patients with asthma and 98 controls were analysed. At baseline, patients were assessed for demographics, atopy, induced sputum profiles and comorbidities including chronic rhinosinusitis (CRS). Serum total IgE and SE‐IgE levels were measured. Asthma severity was assessed on the basis of asthma outcomes during a 12‐month follow‐up period.
Results
At baseline, serum SE‐IgE concentrations were significantly higher in patients with asthma than in controls median 0.16 (interquartile range 0.04–0.53) vs. 0.10 (0.01–0.19), P < 0.001. Elderly asthma patients with high SE‐IgE levels had specific characteristics of having more severe asthma, sputum eosinophilia and CRS, compared to those with lower SE‐IgE levels. In multivariate logistic regression analyses, the associations between serum SE‐IgE concentrations and severe asthma were significant, independently of covariables SE‐IgE‐high (≥ 0.35 kU/L) vs. negative (< 0.10 kU/L) group: odds ratio 7.47, 95% confidence interval 1.86–30.03, P = 0.005. Multiple correspondence analyses also showed that high serum SE‐IgE level had close relationships with severe asthma, CRS and sputum eosinophilia together.
Conclusions and Clinical Relevance
This is the first report on the significant associations of SE‐IgE sensitization with late‐onset asthma in the elderly, particularly severe eosinophilic asthma with CRS comorbidity. Our findings indicate a potential implication of SE in the high morbidity burden of elderly asthma and suggest clues to the pathogenesis of severe late‐onset eosinophilic asthma in the elderly.
We present microlensing events in the 2015 Korea Microlensing Telescope Network (KMTNet) data and our procedure for identifying these events. In particular, candidates were detected with a novel ..."completed-event" microlensing event-finder algorithm. The algorithm works by making linear fits to a grid of point-lens microlensing models. This approach is rendered computationally efficient by restricting u0 to just two values (0 and 1), which we show is quite adequate. The implementation presented here is specifically tailored to the commission-year character of the 2015 data, but the algorithm is quite general and has already been applied to a completely different (non-KMTNet) data set. We outline expected improvements for 2016 and future KMTNet data. The light curves of the 660 "clear microlensing" and 182 "possible microlensing" events that were found in 2015 are presented along with our policy for their public release.
Bone marrow‐derived early endothelial progenitor cells (BM‐EPCs) are a clinical tool for enhancing revascularization. However, the therapeutic efficacy of co‐transplantation of BM‐EPC with islets has ...not been investigated. In this study, marginal mass islets were co‐transplanted with or without BM‐EPCs under the kidney capsules of syngeneic streptozotocin‐induced diabetic mice. Using green fluorescent protein transgenic (GFP‐Tg) mice as BM‐EPC and islet donors or recipients, the role of EPCs in revascularization was assessed for graft morphology, vascular density and fate of EPCs by immunohistochemistry. Islet‐EPC co‐transplantation improved the outcome of islet transplantation as measured by glucose tolerance, serum insulin level and diabetes reversal rate, compared with transplantation of islets alone. Between groups, the morphology of islet grafts showed significant differences in size and composition of grafted endocrine tissues. Significantly more vessel density derived from donors and recipients was detected with islet‐EPC co‐transplantation. Abundant GFP‐Tg mice‐derived BM‐EPCs (GFP‐EPCs) were observed in or around islet grafts and incorporated into CD31‐positive capillaries. Remaining GFP‐EPCs expressed VEGF. In conclusion, co‐transplantation of islets with BM‐EPCs could improve the outcome of marginal mass islet transplantation by promoting revascularization and preserving islet morphology.
Co‐transplantation of bone marrow‐derived early endothelial progenitor cells improves islet graft organization and promotes graft revascularization by both a paracrine effect and direct incorporation into vascular endothelial cells.
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